Dataset Information

How Soluble GARP Enhances TGF? Activation.

ABSTRACT: GARP (glycoprotein A repetitions predominant) is a cell surface receptor on regulatory T-lymphocytes, platelets, hepatic stellate cells and certain cancer cells. Its described function is the binding and accommodation of latent TGF? (transforming growth factor), before the activation and release of the mature cytokine. For regulatory T cells it was shown that a knockdown of GARP or a treatment with blocking antibodies dramatically decreases their immune suppressive capacity. This confirms a fundamental role of GARP in the basic function of regulatory T cells. Prerequisites postulated for physiological GARP function include membrane anchorage of GARP, disulfide bridges between the propeptide of TGF? and GARP and connection of this propeptide to ?v?6 or ?v?8 integrins of target cells during mechanical TGF? release. Other studies indicate the existence of soluble GARP complexes and a functionality of soluble GARP alone. In order to clarify the underlying molecular mechanism, we expressed and purified recombinant TGF? and a soluble variant of GARP. Surprisingly, soluble GARP and TGF? formed stable non-covalent complexes in addition to disulfide-coupled complexes, depending on the redox conditions of the microenvironment. We also show that soluble GARP alone and the two variants of complexes mediate different levels of TGF? activity. TGF? activation is enhanced by the non-covalent GARP-TGF? complex already at low (nanomolar) concentrations, at which GARP alone does not show any effect. This supports the idea of soluble GARP acting as immune modulator in vivo.

SUBMITTER: Fridrich S

PROVIDER: S-EPMC4824412 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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How Soluble GARP Enhances TGFβ Activation.

Fridrich Sven S Hahn Susanne A SA Linzmaier Marion M Felten Matthias M Zwarg Jenny J Lennerz Volker V Tuettenberg Andrea A Stöcker Walter W

PloS one 20160407 4

GARP (glycoprotein A repetitions predominant) is a cell surface receptor on regulatory T-lymphocytes, platelets, hepatic stellate cells and certain cancer cells. Its described function is the binding and accommodation of latent TGFβ (transforming growth factor), before the activation and release of the mature cytokine. For regulatory T cells it was shown that a knockdown of GARP or a treatment with blocking antibodies dramatically decreases their immune suppressive capacity. This confirms a fund ...[more]

PMID: 27054568

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Dataset Information

How Soluble GARP Enhances TGF? Activation.

Publications

How Soluble GARP Enhances TGFβ Activation.

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